AB0654 Elevated Circulating Levels of IL-33 in Systemic Sclerosis Patients with Interstitial Lung Disease
Authors: R. Dacheva, G. Vasilev, K. Tumangelova-Yuzeir, D. Kyurkchiev, S. Monov
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by immune dysregulation, vasculopathy and progressive skin and internal organ fibrosis. Interstitial lung disease (ILD) remains a leading cause of morbidity and mortality in SSc patients. Interleukin 33 (IL-33) is a member of the IL-1 superfamily and has been previously described as a pro-fibrotic cytokine that exerts its function by inducing Th2 cells differentiation and stimulating the expression of TGF-β. Previous reports have revealed the role of IL-33 in numerous fibrotic diseases. Objectives The aim of the present study is to examine the serum levels of IL-33 and explore the possible correlation with clinical and laboratory features with a focus on pulmonary involvement in SSc patients. Methods A total number of fifty five (n=55) patients fulfilling the 2013 ACR/EULAR criteria for classification of SSc were enrolled in the study. Twenty five (n=25) age and sex matched healthy volunteers were used as controls. Detailed medical history, clinical and laboratory parameters were obtained for all included patients. Serum levels of IL-33 (pg/ml) were determined by enzyme-linked immunosorbent assay. GraphPad Prism 6,SPSS V.28 and RStudio were used for the performance of the statistical analysis. Results Of all included patients in the analyses, serum sample was obtained from 55 SSc patients, 51 women (92,7%) and 4 men (7,3%): thirty nine (n=39) with diffuse subset. Mean age was 56±12, mean disease duration was 5.5±6 years. No statistically significant difference was found between IL-33 levels in the patient group and healthy controls. Higher serum IL-33 levels were detected in patients with systemic sclerosis associated interstitial lung disease (SSc-ILD), median 27.9 pg/ml [IQR 4.8-52.9 pg/ml] compared to patients without SSc-ILD 1.12 pg/ml[1.12-45.8 pg/ml]. Decreased percent predicted forced vital capacity (FVC) and vital capacity (VC) correlated inversely with IL-33 levels (p&lt;0,05). The ROC curve analysis with bootstrapping revealed diagnostic accuracy with AUC=0.65, p=0.05 for IL-33 circulating levels as a marker of interstitial lung involvement. A optimal cut-off value of 5 pg/ml was determined with respectively 75 % sensitivity and 60 % specificity. Conclusion IL-33 may be involved in the immunopathogenesis of pulmonary fibrosis. The results are consistent with previous studies. The present study is cross-sectional and further analyses and follow-up may be required to determine whether IL-33 may serve as a potential biomarker in the routine practice. References [1]Yanaba, K., Yoshizaki, A., Asano, Y. Et al. Serume IL-33 levels are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis. Clin. Rheumatol. 30, 825-830 (2011). https://doi.org/10.1007/s10067-011-1686-5 [2] Liew, F., Girard, JP. &amp; Turnquist, H. Interleukin-33 in health and disease. Nat Rev Immunol 15, 676-689 (2016). https://doi.org/10.1038/nri.2016.95 [3]Xu D, Mu R, Wei X. The Roles of IL-1 Family Cytokines in the Pathogenesis of Systemic Sclerosis. Front Immunol. 2019 Sep 13;10:2025. doi: 10.3389/fimmu.2019.02025. PMID: 31572353; PMCID: PMC6753625. DOI: 10.3389/fimmu.2019.02025 Figure 1. Disclosure of Interests Rositsa Dacheva: None declared, Georgi Vasilev: None declared, Kalina Tumangelova-Yuzeir: None declared, Dobroslav Kyurkchiev: None declared, Simeon Monov Speakers bureau: I have been paid as a speaker for AMGEN, PFIZER, NOVARTIS, ABBVIE, ROCHE, ASTRA-ZENECA.